Studies on the mechanisms of bronchogenic carcinoma induction by chemical and physical factors, alone or in various combinations, are pursued in the hamster respiratory carcinogenesis model (Saffiotti, 1968). In vivo studies use two newly established Syrian golden hamster colonies: inbred 15:16/Bio.EHS and outbred Syrian/CG.FOD. Treatments include: intratracheal instillation of carcinogens absorbed on particulate carriers, alone or in combinations; systemic vs/ topical treatments; and combined treatments with carcinogens and co-factors. Respiratory epithelial tissue responses are characterized by histological, ultrastructural, histochemical and biochemical methods, and by their study in organ and cell culture conditions. Light and electron microscopy studies have given preliminary evidence that the respiratory epithelia of very young hamsters contain a large cell population with primitive differentiation that is absent in older animals. The tumor response induced by different carcinogens in different segments of the respiratory tract is being characterized. Among other tumor types, the previously unreported induction of spindle cell carcinomas, a rare tumor type, was obtained with topical administration of N-methyl-N-nitrosourea. Regionally selective toxic agents are investigated; the toxic effects of 3-methylindole and 2-methylnaphthalene (two components of cigarette smoke with selective toxicity for Clara cells and alveolar type I cells in certain species) have been studied in the hamster model.